Layered mafic intrusions represent an important aspect of magmatism on earth and have occurred from Archean to present times. Literature on the geochemistry and petrology of these intrusions abounds but their physical properties, which could provide significant constraints on their formation, have seldom been investigated. Classic petrological methods such as whole-rock geochemistry, textural analysis and mineral chemistry have been applied to several intrusions of various ages. Most of these methods are relatively expensive or time intensive which limits high resolution studies. On the contrary, magnetic methods are typically inexpensive and fast and have been successfully applied to various occurrences of mafic rocks. In this study, several magnetic methods have been applied to a 600 m-long continuous borehole core drilled through one of the world's largest layered mafic intrusion, the Great Dyke of Zimbabwe. The main goal of this study is to constrain the magmatic history of the intrusion. More specifically, it is important to determine if the intrusion functioned as an open system, characterized by multiple magma pulses, or as a closed system, undergoing differentiation after a single magmatic pulse. The magnetic methods have also been validated by other independent approaches including image analysis, and electron microprobe. This study demonstrates that magnetic methods can be used to rapidly obtain critical information on the internal structure of this type of intrusion before applying more costly chemical analyses. The main scientific result of this study is to document the closed system nature of the Great Dyke of Zimbabwe, at least throughout the sequence investigated.

The composition of meteorites and the surface of asteroids suggest that planetesimals of the early solar system have undergone partial melting and differentiation. The sepa- ration of the denser metal (Fe-FeS alloy) from the lighter silicate is the most important differentiation process. The melting is mainly induced by the heat produced through the decay of 26Al and 60Fe. The distribution of these heat sources inside the celestial body is not uniform. In fact, 26Al is a lithophile element following the migration of the silicate and 60Fe is a siderophile element following the metal. In modeling the differen- tiation of small bodies it is fundamental to include at least two fluid phases in addition to the solid matrix. This study presents a first time three-phase mixture model for the metal-silicate segregation in a compacting body. The theoretical model is developed fol- lowing the classical averaging approach. The governing equations are then implemented in a numerical model in 1-D spherical geometry. In presence of two fluids, these can exchange their position within the porous matrix even in absence of compaction. They also act a mutual viscous drag force, which results in small fractions of metal to ascend with the lighter silicate, and viceversa. / <p>Validerat; 20151008 (global_studentproject_submitter)</p>

No description available.

In the mammalian bloodstream, the protozoan parasite Trypanosoma brucei undergoes differentiation from proliferative slender forms to arrested, transmissible, stumpy forms. This transition is associated with extensive cytological and metabolic changes that promote survival in the tsetse midgut, and also influences infection dynamics within the mammalian host. A number of genes involved in this transformation were recently identified using an RNAi library screen for resistance to pCPTcAMP, a membrane-permeable cyclic AMP analogue that induces differentiation. These molecules, referred to here as posST (positive mediators of STumpy formation), were thereafter validated to regulate the slender to stumpy transition, with many of them apparently comprising part of a signal transduction and effector pathway. However, it is unknown how these proteins act in relation to one another or are ordered within the pathway. To this end, null mutants were created for several posST components in differentiation-competent pleomorphic trypanosomes and, in this genetic background, other members of the predicted pathway expressed to test their ability to restore stumpy formation. Analysis of distinct combinations has been used to build a preliminary pathway structure model for the signalling events underlying trypanosome quorum sensing. In addition, phosphoproteomic analysis of two null mutants has revealed downstream signalling effects of two posST kinases, MEKK1 and YAK. A similar extragenic suppression approach was also applied to explore the interaction between the identified drivers of stumpy formation and the target of rapamycin kinase, TOR4, which has previously been shown to act as a negative regulator of stumpy formation in monomorphs. Dual ablation of TOR4 and posST components revealed insight into the intersection of stumpy-promoting and stumpy-inhibiting pathways. Finally, a chemical-genetic approach was used to investigate the posST pathway using two differentiation-inducing compounds: the previously studied E667, and GKI7, newly identified from a kinase inhibitor set. RNAi lines for different posST components were tested for their ability to undergo development in the presence of these compounds. An RNAi library screen using GKI7 identified putative new mediators of stumpy formation.

Many cellular functions depend on the tightly regulated expression of various proteins. Canonical control of the protein expression is associated with transcriptional regulation. However, the small non-coding RNAs called microRNAs (miRNAs) were identified as post-transcriptional regulators of gene expression. In a typical manner, miRNAs originate similarly to the coding RNAs and are processed in a multi-step maturation process. It has been shown that miRNAs are very important for the proper functioning of tissues. Interestingly, the human nervous system contains over 70% of all miRNAs; thus, the maturation process has to be tightly regulated. However, despite the important role of miRNAs, little is known about the mechanisms regulating their biogenesis. In my PhD project, I showed that during early stages of neuronal differentiation, Lin28a controls levels of neuro-specific miRNA-9. I demonstrated that Lin28a binds to the conserved terminal loop (CTL) of pre-miRNA-9 and decreases the cellular levels of miRNA-9 during retinoic acid-mediated neuronal differentiation of mouse teratocarcinoma P19 cells. I revealed that the Lin28a-mediated inhibition of miRNA-9 production was uridylation-independent. Furthermore, constitutive expression of GFP-tagged Lin28a reduced the levels of let-7a but not miRNA-9, whereas untagged Lin28a inhibited both miR-9 and let-7a during the course of neuronal differentiation. Using small RNAseq analysis of P19 cells with constitutive expression of Lin28a I showed that it controls many more miRNAs than previously recognised. Intriguingly, many miRNAs were upregulated by Lin28a overexpression. I demonstrated with high-throughput, the limited function of GFP-tagged Lin28a results, and I also showed that untagged Lin28a inhibits the production of a number of brain-specific miRNAs including miRNA-9. Finally, I revealed that 3’-5’exoribonuclease Dis3l2 was responsible for uridylation-independent degradation of pre-miRNA-9. Altogether, my results provided evidence that Lin28a has both positive and negative roles in the regulation of miRNA production and has a dual role in triggering pre-miRNA degradation.

Orientador: Francisco Haiter Neto / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-21T22:06:49Z (GMT). No. of bitstreams: 1 Gamba_ThiagodeOliveira_M.pdf: 1982337 bytes, checksum: 59e9e9eb3c74854ff87b24acbb1ed82a (MD5) Previous issue date: 2013 / Resumo: O objetivo no presente estudo foi verificar se medidas antropológicas realizadas em mandíbulas, por meio de imagem de Tomografia Computadorizada de feixe cônico (TCFC), podem detectar o dimorfismo sexual em uma população brasileira. Adicionalmente, criar uma fórmula, a partir destas medidas para determinação do sexo. Para isso, foi selecionada uma amostra de 159 imagens de TCFC de indivíduos de uma população brasileira (74 homens e 85 mulheres), com idade variando de 18 a 60 anos. As imagens foram analisadas por 5 avaliadores, que realizaram seis mensurações: comprimento do ramo mandibular em altura (CR), comprimento da base mandibular (CBM), menor comprimento do ramo mandibular em largura (MCR), ângulo goníaco (AG), distância intercondilar (DIC) e distância intergoníaca (DIG), em reconstruções 3D de TCFC. Após quinze dias, as mensurações foram repetidas com 25 % da amostra. Para análise estatística, foi aplicada a Correlação Intraclasse na avaliação intra e interexaminador, Análise de Variância (ANOVA) para comparação entre os valores médios das mensurações presentes e equações binárias de Regressão Logística foram criadas para determinação do sexo. As mensurações evidenciaram valores do sexo masculino superiores aos do feminino, exceto na variável MCR que não apresentou diferença estatisticamente significante entre os sexos. As medidas com maiores índices dimórficos foram: DIG, CR, DIC, e AG. Associando estas quatro medidas obteve-se uma precisão de 95,1% na determinação do sexo, assim, foi possível concluir que a fórmula desenvolvida no presente estudo pode ser utilizada para identificação do sexo na prática forense / Abstract: The aim of this study was to determine whether anthropological measurements taken in jaws through image cone beam CT (CBCT) could aid in detecting sexual dimorphism in a Brazilian population. Additionally, this study was aimed at creating a formula from these measurements for sex determination. Subjects (n=159) involved a Brazilian population (74 men and 85 women), aged 18-60 years. The CBCT images were analyzed by 5 reviewers, who performed six measurements in the analysis of sexual dimorphism: Ramus length (R-L); Gonion-gnathion length (G-G-L); Minimum ramus breadth (M-R-Br); Gonial angle (G-A); Bicondylar breadth (Bic-Br); and Bigonial breadth (Big-Br), reconstructions in 3D CBCT. The measurements were repeated with 25% of the sample 15 days after the first evaluation for statistical analysis, the intraclass correlation was used to evaluate intra- and inter-examiners, the Analysis of Variance (ANOVA) to compare the mean values and the binary logistic regression equations were created to determine the sex. The measurements showed higher values for males, except for M-R-Br, showing no statistically significant difference between genders. The measurements with the highest rates were dimorphic: Big-Br, R-L, Bic-Br and GA. When the four variables were associated, an accuracy of 95.1% in sex determination was observed. In conclusion, the formula developed in this study can be used for sexual differentiation in forensic settings / Mestrado / Radiologia Odontologica / Mestre em Radiologia Odontológica

The human colonic carcinoma cell lines HT-29 and Caco-2 both exhibit structural and functional differentiation under appropriate culture conditions. HT-29 can be induced to differentiate by treatment with short-chain fatty acids or acetoacetate. Caco-2 cells differentiate spontaneously upon contact inhibition. In this study HT-29 cells were treated with 5 mM acetate, propionate, butyrate and acetoacetate (physiological inducers) to assess their effects on the expression of carbonic anhydrase 1, sucrase-isomaltase and alkaline phosphatase which are reported to be markers of gastrointestinal differentiation. The maturation induction observed was compared to that of the spontaneous differentiation observed in Caco-2 cells. Assays were performed over an 18 day period. Results showed a close correlation (p < 0.05) between HT-29 and Caco-2 cell on days 4 and 12. These results indicate that differentiation reported in both cell lines is comparable and can be used as a basis for further comparative studies. In addition, parallel experiments to the above were conducted using a selection of nine rationally designed cyclic dipeptides (CDPs) potential drug entities which were chosen as non-physiological inducers. The results showed that the cyclic dipeptides were able to induce the gastrointestinal phenotype as observed in HT-29 cells treated with physiological inducers. Studies on the effects of energy-related metabolism in HT-29 and Caco-2 cells as induced by physiological and non-physiological inducers indicated that energy metabolism is a significant role player in gastrointestinal differentiation. The results reported show a decrease in ATP concentrations indicating that the cyclic dipeptides, like physiological inducers, affect the energy state of the HT-29 cells and thus may effect the differentiation of these cells. A positive correlation was found between histone phsophorylation and differentiation confirming that histone phsophorylation was partly responsible for the decrease in ATP concentrations. It is suggested that the induction of differentiation in HT- 29 cells could be either due to non-specific transcription of genes by activation of a chromatin switch or specific by the activation of signal transduction pathways based on the flux of ATP through the cells. Differential display RT-PCR is probably the most sensitive method that could be used to validate the suggestion of either a nonspecific transcription of genes or a specific differentiation reported for HT-29 cells.

Ecological differentiation and adaptation are processes that can drive divergence and speciation. Measuring ecologically revenant traits can help to identify possible targets of natural selection that may have mediated ecological differentiation. This study looked for evidence of within and between species differentiation in seven ecologically relevant traits in two closely related species sampled across their range, and whether any of these traits were related to climate differences among site of origin. We measured seven traits under common garden conditions in seedlings of Silene dioica (11 populations, n=528) and Silene latifolia (14 populations, n=672) grown in the botanical garden in Uppsala in a randomised block design. Three traits related to leaf morphology were measured, and four related to water usage of the plant were measured. These traits were analysed for differences between the species as well as for differences within each species between populations using a linear mixed model. The traits’ relationship to a climate variable, derived from the axes of a principal components analysis of climate data for each site, was investigated using a linear model. A number of drought avoidance (e.g. succulence, max turgid weight) and morphological traits (e.g. leaf ratio) differed between the two species. Water use efficiency has been flagged before as possibly driving ecological differentiation between the two species and the results identify possible candidate traits for quantifying this separation. Differentiation between populations within each species was also present in two traits within S. latifolia and in four traits within S. dioica significantly varying between the populations. This could reflect either local adaptation or genetic drift acting on populations across the range. One trait related to the amount of water taken up by the leaf (wgain) was found to be significantly associated with the climate variable, which was extracted from the principal components analysis, in S. latifolia. The results identified a number of candidate traits which could reflect ecological differences between the species especially with respect to water relations. These traits may allow the species to respond differently during periods of water stress, which in turn could result in ecological separation of the species and determine their geographical ranges.

Candida albicans is a polymorphic yeast that can cause life threatening systemic infections in immuno-compromised individuals. One key attribute of C. albicans that enhances its pathogenicity is the ability to switch morphologies between filamentous and vegetative modes in response to specific environmental conditions. Stressful changes in such cellular conditions commonly cause a rapid inhibition of global protein synthesis leading to altered programmes of gene expression. In Saccharomyces cerevisiae, fusel alcohols signal nitrogen scarcity and induce pseudohyphal growth enabling yeast colonies to spread towards nutrient replete areas. These alcohols also inhibit protein synthesis by targeting the translation initiation factor, eIF2B. eIF2B is the guanine nucleotide exchange factor for eIF2, which supports eIF2-GTP production and represents a key regulated step in translation initiation. eIF2-GTP interacts with Met-tRNAiMet to form the ternary complex which is essential for translation initiation. Fusel alcohols target eIF2B leading to reduced levels of ternary complex and reduced protein synthesis. In Candida albicans, a variety of cell biological and genetic assays suggest that fusel alcohols and ethanol inhibit protein synthesis by targeting the translation initiation factor, eIF2B, and they also induce hyphal/pseudohyphal growth, a process that is associated with pathogenesis in C. albicans. In contrast to fusel alcohols, farnesol, aquorum sensing alcohol, does not appear to impact upon eIF2B activity. Rather, biochemical and mass spectrometric analysis suggest farnesol affects the interaction of the mRNA with the small ribosomal subunit during translation initiation. Further elucidation of the effect of farnesol on C. albicans transcript levels and ribosome association by next generation sequencing gave insight into the genes that are differentially expressed following farnesol treatment. While genes involved inmorphological differentiation were generally repressed, those involved in protein synthesis were upregulated, possibly as an adaptive response to inhibition of protein synthesis by farnesol. Intriguingly, the regulation of these functional categories of genes occurred in a co-ordinated manner at either the transcript level or at the level of ribosome association, but rarely was gene expression regulated at both transcriptional and post-transcriptional levels for the same gene.

The classical model of sexual differentiation states that genes influence gonadal differentiation, and gonadal hormones then drive sexual differentiation throughout development. This model has been called into question by research, especially in songbirds, providing evidence for alternative mechanisms like direct effect of genes and local production of steroids via de novo synthesis or local metabolism of steroid precursors like DHEA, which can be metabolized to testosterone and E₂. In order to assess the role of local steroid production on sexual differentiation in songbirds, levels of DHEA and E₂ were measured in brachial and jugular plasma, as well as brain and peripheral tissues in zebra finches at critical ages during development and in adulthood. DHEA levels in brachial and jugular plasma peaked at P30 and higher DHEA levels in jugular plasma were found in males relative to females at P30. Also, at P30, higher DHEA levels were found in rostral telencephalon in females relative to males. The findings of this study indicate that DHEA may play a role in sexual differentiation of songbirds. Surprisingly, E₂ was non-detectable in many plasma and tissue samples. Higher E₂ was found in the diencephalon in females relative to males at P3/P4 and higher E₂ was found in gonads in adult females relative to males. There was little evidence to suggest that E₂ is synthesized de novo in the brain, although perhaps E₂ is being rapidly metabolized into another estrogen or E₂ synthesis is more localized in the synapse. The findings of this study support the role of alternative mechanisms like de novo steroid synthesis and local metabolism of steroid precursors and challenge the role of classical mechanisms of sexual differentiation in songbirds. Also, these findings may have important implications for sex differences, which develop independently of gonadal hormones, in other animal species. / Medicine, Faculty of / Graduate